Researchers make significant progress in engineering digestive system tissues
Wake Forest Baptist Medical Center News Jul 12, 2017
Reporting in the journal Stem Cells Translational Medicine, the research team at Wake Forest Institute for Regenerative Medicine verified the effectiveness of lab–grown anal sphincters to treat a large animal model for fecal incontinence, an important step before advancing to studies in humans. And in the journal Tissue Engineering, the team reported success implanting human–engineered intestines in rodents.
ÂResults from both projects are promising and exciting, said Khalil N. Bitar, PhD, AGAF, senior researcher on the projects, and professor of regenerative medicine at the institute.
Sphincter Project: The lab–engineered sphincters are designed to treat passive incontinence, the involuntary discharge of stool due to a weakened ring–like muscle known as the internal anal sphincter. The muscle can lose function due to age or can be damaged during child birth and certain types of surgery, such as cancer.
Current options to repair the internal anal sphincter include grafts of skeletal muscle, injectable silicone material or implantation of mechanical devices, all of which have high complication rates and limited success.
ÂThe regenerative medicine approach has a promising potential for people affected by passive fecal incontinence, said Bitar. ÂThese patients face embarrassment, limited social activities leading to depression and, because they are reluctant to report their condition, they often suffer without help.Â
BitarÂs team has been working to engineer replacement sphincters for more than 10 years. The current study involved 20 rabbits with fecal incontinence. Eight animals were treated with sphincters engineered from their own muscle and nerve cells, eight animals were not treated and four received a Âsham surgery.
The sphincters were engineered using small biopsies from the animals sphincter and intestinal tissue. From this tissue, smooth muscle and nerve cells were isolated and then multiplied in the lab. In a ring–shaped mold, the two types of cells were layered to build the sphincter. The entire process took about four to six weeks.
In the animals receiving the sphincters, fecal continence was restored throughout a three month follow–up period, compared to the other groups, which did not improve. Measurements of sphincter pressure and tone showed that the sphincters were viable and functional and maintained both the muscle and nerve components. Currently, longer follow up of the implanted sphincters is close to completion with good results.
Intestine Project: ÂA major challenge in building replacement intestine tissue in the lab is that it is the combination of smooth muscle and nerve cells in gut tissue that moves digested food material through the gastrointestinal tract, said Bitar.
Through much trial and effort, his team has learned to use the two cell types to create Âsheets of muscle pre–wired with nerves. The sheets are then wrapped around tubular molds made of chitosan, a natural material derived from shrimp shells. The material is already approved by the U.S. Food and Drug Administration for certain applications.
In the current study, the tubular structures were implanted in rats in two phases. In phase one, the tubes were implanted in the omentum, which is fatty tissue in the lower abdomen, for four weeks. Rich in oxygen, this tissue promoted the formation of blood vessels to the tubes. During this phase, the muscle cells began releasing materials that would eventually replace the scaffold as it degraded.
For phase two, the bioengineered tubular intestines were connected to the animals intestines, similar to an intestine transplant. During this six–week phase, the tubes developed a cellular lining as the bodyÂs epithelial cells migrated to the area. The rats gained weight and studies showed that the replacement intestine was healthy.
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ÂResults from both projects are promising and exciting, said Khalil N. Bitar, PhD, AGAF, senior researcher on the projects, and professor of regenerative medicine at the institute.
Sphincter Project: The lab–engineered sphincters are designed to treat passive incontinence, the involuntary discharge of stool due to a weakened ring–like muscle known as the internal anal sphincter. The muscle can lose function due to age or can be damaged during child birth and certain types of surgery, such as cancer.
Current options to repair the internal anal sphincter include grafts of skeletal muscle, injectable silicone material or implantation of mechanical devices, all of which have high complication rates and limited success.
ÂThe regenerative medicine approach has a promising potential for people affected by passive fecal incontinence, said Bitar. ÂThese patients face embarrassment, limited social activities leading to depression and, because they are reluctant to report their condition, they often suffer without help.Â
BitarÂs team has been working to engineer replacement sphincters for more than 10 years. The current study involved 20 rabbits with fecal incontinence. Eight animals were treated with sphincters engineered from their own muscle and nerve cells, eight animals were not treated and four received a Âsham surgery.
The sphincters were engineered using small biopsies from the animals sphincter and intestinal tissue. From this tissue, smooth muscle and nerve cells were isolated and then multiplied in the lab. In a ring–shaped mold, the two types of cells were layered to build the sphincter. The entire process took about four to six weeks.
In the animals receiving the sphincters, fecal continence was restored throughout a three month follow–up period, compared to the other groups, which did not improve. Measurements of sphincter pressure and tone showed that the sphincters were viable and functional and maintained both the muscle and nerve components. Currently, longer follow up of the implanted sphincters is close to completion with good results.
Intestine Project: ÂA major challenge in building replacement intestine tissue in the lab is that it is the combination of smooth muscle and nerve cells in gut tissue that moves digested food material through the gastrointestinal tract, said Bitar.
Through much trial and effort, his team has learned to use the two cell types to create Âsheets of muscle pre–wired with nerves. The sheets are then wrapped around tubular molds made of chitosan, a natural material derived from shrimp shells. The material is already approved by the U.S. Food and Drug Administration for certain applications.
In the current study, the tubular structures were implanted in rats in two phases. In phase one, the tubes were implanted in the omentum, which is fatty tissue in the lower abdomen, for four weeks. Rich in oxygen, this tissue promoted the formation of blood vessels to the tubes. During this phase, the muscle cells began releasing materials that would eventually replace the scaffold as it degraded.
For phase two, the bioengineered tubular intestines were connected to the animals intestines, similar to an intestine transplant. During this six–week phase, the tubes developed a cellular lining as the bodyÂs epithelial cells migrated to the area. The rats gained weight and studies showed that the replacement intestine was healthy.
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